The determination of the concentration of various analytes in physiological samples is of growing importance in our society. Such samples are analyzed in various fields of application e.g. in clinical laboratories or in home monitoring. In this connection the results are of major importance for the treatment of various diseases. This also especially includes the measurement of glucose in diabetes management and the measurement of cholesterol in the case of cardiac and vascular diseases. Medical blood diagnostics typically requires the collection of a blood sample from the individual to be examined.
The analytics carried out after the blood collection process are often carried out in a small, portable measuring device, a so-called handheld device in which test elements wetted with blood are analyzed. These handheld devices are of major importance especially in the diagnosis of diabetes diseases. In these devices the measurement is primarily carried out electrochemically or optically. In the case of optically-based measurements, the sample is illuminated with light and the reflected light is detected in order to determine the analyte concentration. Test elements such as test strips are primarily used for this which are wetted with the sample such as blood or interstitial fluid on a detection area which is part of the test element. The sample subsequently reacts with the reagents which are applied in or on the detection area. This can lead to a change in color or also in the case of an electrochemical reaction to changes in charge which can then be detected.
In the case of an optical evaluation of detection areas on which only small amounts of sample have been applied, it is very important that the wetted area of the detection area is optimally evaluated. This can be achieved by using reference areas, in addition to an adequate illumination and detection. The referencing can be carried out in various ways. Thus, a reference area which is separated from the detection area can be used thus enabling technical effects such as the properties of the light source or of the detector as well as certain properties of the test element to be compensated. In order to be able to carry out a referencing with regard to sample properties, the reference area should have a similar construction to the detection area.
One example of referencing in a reflectometric system for determining light intensities of a colored spot uses the area surrounding the spot for referencing. The disadvantage of this method is that the background signal for referencing is not wetted by the sample and therefore has other optical properties than the area wetted with sample. One exemplary disclosure in this regard is U.S. Patent Application Publication No. 2004/0071331.
In other methods for determining an analyte concentration in a sample, a distinction is made between two subareas having different binding activities to the analyte in the sample. A binding partner carrier is immobilized in the subarea having a higher binding activity which binds the analyte when the sample is applied. No binding partner is immobilized on the carrier in the subarea with less binding activity towards the analyte. The area with less binding activity is used for referencing. A disadvantage of this analytical system is that with this analytical method it is only possible to carry out and reference reactions which require binding of the analyte to a carrier-immobilized binding partner such that diffusion of the analyte is no longer possible. The determination of the analyte is limited to bound molecules. An exemplary disclosure in this regard is EP 0 469 377.
In yet another referencing method relating to a system for detecting an analyte on a test carrier, the analyte is bound to a receptor immobilized on the test carrier. Part of the test carrier which contains no immobilized receptor is used as a reference. In some instances, the determination of the analyte requires a binding to an immobilized component. An exemplary disclosure in this regard is issued U.S. Pat. No. 6,249,593.
Based on the disadvantages of the prior art, it is an object of the present invention to provide an analytical system for determining the concentration of an analyte which requires no irreversible binding of the analyte to the test carrier.
Another object of the present invention is to provide an analytical system which enables a more accurate determination of analytes using very small sample volumes.